Immunoglobulin subclass profiles of anti-idiotypic antibodies to GAD65Ab differ between type 1 diabetes patients and healthy individuals.

Previously we reported the presence of anti-idiotypic antibodies (anti-Id)-specific to autoantibodies against GAD65 (GAD65Ab) in healthy individuals while the activity of anti-Id directed to GAD65Ab in type 1 diabetes (T1D) patients was significantly lower. These anti-Id recognize the antigen-binding site of GAD65Ab, thus preventing their binding to GAD65. Here, we characterized the IgG subclass profile of these anti-Id (GAD65Ab specific) and of the associated GAD65Ab themselves. The IgG subclass response of anti-Id in healthy individuals (n = 16) was IgG3-dominated, while in T1D patients (n = 8) IgG1 was the major IgG subclass. The GAD65Ab bound by anti-Id in both healthy individuals (n = 38) and GAD65Ab-negative T1D patients (n = 35) showed a predominant rank order of IgG1 > IgG2 > IgG4 > IgG3. However, the frequency of GAD65Ab of the IgG4 subclass was significantly higher in T1D patients (P < 0.05). We conclude that the IgG subclass profile of anti-Id (GAD65Ab specific) in healthy individuals differs from that in T1D patients. These differences may provide insights into the development of these antibodies.